High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33
High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33
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DOI：
10.1038/sj.gene.6364295
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发表时间：
2006-06-01
影响因子：
5
通讯作者：
Gregersen, P. K.
中科院分区：
文献类型：
--
作者：
Amos, C. I.;Chen, W. V.;Gregersen, P. K.
我们已经完成了一个全基因组的连锁扫描，使用> 5700个信息单核苷酸多态性（SNP）标记（Illumina IV SNP连锁面板）在642个高加索家庭中包含受影响的同胞对类风湿性关节炎（RA），由北美风湿性关节炎协会确定。结果表明，在染色体2q33和11p12的连锁与对数的优势（LOD）得分分别为3.52和3.09，显着的新证据。除了围绕主要组织相容性复合体（LOD > 16）的强而宽的连锁区间外，在5号和10号染色体上观察到LOD > 2.5的区域。在第4、7、12、16和18号染色体上也观察到其他连锁证据（LOD评分在1.46和2.35之间）。多个区域遗传连锁的新证据部分解释了Illumina IV SNP连锁面板（75.6%）与以前使用的标准微卫星连锁面板（平均52.6%）相比显着增加的信息内容。根据同胞对成员是否显示升高的抗环瓜氨酸肽滴度进行的分层分析表明，染色体4、5、6和7上的层之间连锁的证据存在显著变化。总的来说，这些新的连锁数据应该重振努力，利用位置信息，以确定RA的易感基因。
We have completed a genome wide linkage scan using > 5700 informative single-nucleotide polymorphism (SNP) markers (Illumina IV SNP linkage panel) in 642 Caucasian families containing affected sibling pairs with rheumatoid arthritis (RA), ascertained by the North American Rheumatoid Arthritis Consortium. The results show striking new evidence of linkage at chromosomes 2q33 and 11p12 with logarithm of odds (LOD) scores of 3.52 and 3.09, respectively. In addition to a strong and broad linkage interval surrounding the major histocompatibility complex (LOD > 16), regions with LOD > 2.5 were observed on chromosomes 5 and 10. Additional linkage evidence (LOD scores between 1.46 and 2.35) was also observed on chromosomes 4, 7, 12, 16 and 18. This new evidence for multiple regions of genetic linkage is partly explained by the significantly increased information content of the Illumina IV SNP linkage panel (75.6%) compared with a standard microsatellite linkage panel utilized previously (mean 52.6%). Stratified analyses according to whether or not the sibling pair members showed elevated anticyclic citrullinated peptide titers indicates significant variation in evidence for linkage among strata on chromosomes 4, 5, 6 and 7. Overall, these new linkage data should reinvigorate efforts to utilize positional information to identify susceptibility genes for RA.